The invention provides new methods for treating against apoptotic cell death, including apoptotic cardiac and neuronal cells. Therapies of the invention include administration of a mitochondrial oxidizer compound to a subject in need thereof, such as a subject suffering from or susceptible to stroke, heart attack, brain or spinal cord trauma, or chronic conditions that can result in apoptotic cell death such as neurodegenerative disease.
Acute ischemic syndromes, notably heart attack and stroke, remain the leading causes of death and disability in developed countries.
Nerve cell death (degeneration) can cause potentially devastating and irreversible effects for an individual and may occur e.g. as a result of stroke, heart attack or other brain or spinal cord ischemia or trauma. Additionally, neurodegenerative disorders involve nerve cell death (degeneration) such as Alzheimer""s disease, Parkinson""s disease, Huntington""s disease, Amyotrophic Lateral Sclerosis, Down""s Syndrome and Korsakoff""s disease.
It would be desirable to have new therapies for treatment against such indications.
We now provide therapies for treatment against apoptotic cell death. In particular, we have discovered that mitochondrial KATP channel activation can effectively inhibit apoptosis in a variety of cells, including cardiac and neuronal cells.
Methods of the invention include treatment of mammalian cells, particularly primate cells especially human cells with one or more compounds that can modulate mitochondrial function, particularly compounds that can positively impact mitochondrial function and increase cell energy output. Such compounds are referred to herein as xe2x80x9cmitochondrial oxidizer compoundsxe2x80x9d or xe2x80x9cmitoKATP channel opening compoundsxe2x80x9d or other similar term and can be identified e.g. by assays disclosed herein as well as in U.S. Pat. No. 6,183,948 to Marban et al. Specifically preferred mitoKATP channel opening compounds for use in the methods of the invention include diazoxide, pinacidil, nicorandil, and BMS 191095, or compounds which confer protection that can be inhibited by 5-hydroxydecanoate (a mitoKATP antagonist).
Methods of the invention particularly include treating cells that are apoptotic or otherwise undergoing programmed cell death, or at risk to undergo such programmed cell death. Ventricular cells and neuronal cells are particularly suitable for treatment in accordance with the invention. For example, a subject suffering from or susceptible to heart failure can be treated in accordance with the invention. Additionally, a subject suffering from a condition involving programmed cell death of neuronal cells can be treated in accordance with the invention, particularly to treat a subject suffering from stroke, spinal cord injury or a neurodegenerative disease such as Alzheimer""s disease, Parkinson""s disease, Huntington""s disease, Amyotrophic Lateral Sclerosis, Down""s Syndrome, Korsakoff""s disease, cerebral palsy and/or age-dependent dementia.
Still further, the invention includes treatment of diabetes, including treatment of pancreatic beta cells, apoptosis of which can be involved with a subject suffering from diabetes.
Treatment methods of the invention include administration to a mammal in need of such treatment a therapeutically effective amount of one or more compounds that can positively impact mitochondrial function (i.e. mitoKATP channel opening compounds) to an animal, including a mammal, particularly a human. Preferably, a subject is identified and selected that is susceptible to or suffering from a condition associated with apoptotic cell death.
Other aspects of the invention are disclosed infra.